Mechanisms of muscle steatosis in dysferlinopathy: relationship to interaction of dysferlin and PTRF

Abhimanyu Garg, MD and Anil Agarwal, Ph.D.

University of Texas Southwestern Medical Center (Dallas, TX)

Abhimanyu Garg, MD is a Professor of Internal Medicine and Chief of the Division of Nutrition and Metabolic Diseases at the University of Texas Southwestern Medical Center in Dallas, Texas. He holds a Distinguished Chair in Human Nutrition Research. Anil Agarwal is also a Professor of Internal Medicine in the Division of Nutrition and Metabolic Diseases at the University of Texas Southwestern Medical Center.

Research Projects

Objective: 
The first objective of our study is to explore the underlying mechanisms as to how excessive lipids (fat or triglycerides) accumulate in the muscle of dysferlin-deficient mice and humans. The second objective is to define how the deficiency of Cavin-1 protein (also known as PTRF), which plays a role in forming caveolae (small invaginations on the cell membrane), affects the function and subcellular localization of dysferlin (DYSF) in mice and in human.

We have been engaged for last several years in exploring and understanding how loss of protein(s) leads to loss of adipose tissue, both in animal models and in humans and have developed tools to explore the biology of fat in tissues like the liver and muscle. From this perspective, we have designed experiments to determine why a few muscles, like psoas, in dysferlin-deficient mice, accumulate lipids and to measure the deleterious effect of lipid accumulation in muscle function. We will also study how additional protein(s) interact with dysferlin protein and cause muscle dysfunction in mice and humans with dysferlin-deficiency.  Such studies will define two important aspects: a) molecular mechanism(s) for muscle lipid accumulation and b) protein partners of dysferlin, aiding in further designing the therapeutic approaches for the treatment of patients with dysferlinopathy.